Fluorine-containing dicarbonyl compounds, such as 2-fluoro-3-oxoalkylcarboxylic acid esters, are compounds of significant usefulness suitable for use as an intermediate for the production of pharmaceutical products and agricultural chemicals.
One way to produce these compounds is by directly fluorinating corresponding dicarbonyl compounds with fluorine gas. Examples of such techniques are described, for example, in J. Org. Chem. 57(1992): 2196, International Patent Publication Nos. WO 94/10120 and WO 95/14646, and Japanese Patent Laid-Open Publication No. Hei 09-255611. In each of these techniques, the goal is to selectively obtain a desired fluorine-containing dicarbonyl compound, such as the 2-fluoro-3-oxoalkylcarboxylic acid ester, and each technique involves directly fluorinating corresponding dicarbonyl compounds with fluorine gas.
However, the direct fluorination of a dicarbonyl compound with fluorine gas is a process involving free radicals and it is therefore difficult to selectively obtain only desired fluorine-containing dicarbonyl compound, such as the 2-fluoro-3-oxoalkylcarboxylic acid ester. For instance, the fluorination reaction described in the cited articles results in the generation of mono-fluoro forms, di-fluoro forms, and compounds containing more fluorine atoms.
In each of the techniques described in the cited articles, water is added to the reaction mixture after the fluorination reaction and the mixture is then extracted with dichloromethane. Nevertheless, none of the cited articles specifically describe any technique for purifying/separating a desired fluorine-containing dicarbonyl compound, such as the 2-fluoro-3-oxoalkylcarboxylic acid ester.
Using a known distillation technique, the present inventors have previously made attempts to separate the desired product from the reaction mixture, only to learn that the purification was difficult since the 3-oxoalkylcarboxylic acid esters, once fluorinated, readily degrade. Thus, there has been no choice other than to directly use the fluorinated 3-oxoalkylcarboxylic acid esters in the subsequent processes without distilling/purifying the reaction mixture. In a technique disclosed in European Patent No. 0440372A1, for example, a 2-fluoro-3-oxoalkylcarboxylic acid ester is reacted with amidine to produce a triazole derivative, a known fungicide. When this 2-fluoro-3-oxoalkylcarboxylic acid ester contains significant amounts of impurities, the purity of the reaction product is lowered and the generation of compounds of unknown structure is likely to result. Also, the low purity material significantly limits the reaction conditions and thus makes the production process difficult.